title: BCR-ABL1 kinase domain mutations may persist at very low levels for many years and lead to subsequent TKI resistance.
abstract: BACKGROUND
  BCR-ABL1 mutation analysis is recommended for chronic myeloid leukaemia patients. However, mutations may become undetectable after changing therapy, and it is unknown whether they have been eradicated.
  
  
  METHODS
  We examined longitudinal data of patients with imatinib-resistant mutations, which became undetectable by Sanger sequencing to determine whether mutations could reappear, and the related circumstances.
  
  
  RESULTS
  Identical imatinib- and nilotinib-resistant mutations reappeared following further therapy changes in five patients, and was associated with subsequent nilotinib resistance in four.
  
  
  CONCLUSIONS
  The data suggest that some BCR-ABL1 mutations may persist at undetectable levels for many years after changing therapy, and can be reselected and confer resistance to subsequent inhibitors.
authors.affiliation: Department of Molecular Pathology, Centre for Cancer Biology, SA Pathology, Adelaide, South Australia, Australia.
authors.forename: W T
authors.initials: WT
authors.lastname: Parker
authors.forename: A L
authors.initials: AL
authors.lastname: Yeoman
authors.forename: B A
authors.initials: BA
authors.lastname: Jamison
authors.forename: D T
authors.initials: DT
authors.lastname: Yeung
authors.forename: H S
authors.initials: HS
authors.lastname: Scott
authors.forename: T P
authors.initials: TP
authors.lastname: Hughes
authors.forename: S
authors.initials: S
authors.lastname: Branford
mesh_terms: D000328:Adult; D000368:Aged; D001549:Benzamides / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology; D012189:Retrospective Studies
chemical_list: C581634:BCR-ABL1 fusion protein, human; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; C498826:nilotinib